deviations for the S22 benchmark set of noncovalent interactions for 11 std. We have developed a highly parallelized QM/MM implementation in the NAMD and OpenAtom simulation packages, using the dual grid, dual length scale method for combined plane-wave and Euler exponential spline-based QM/MM simulations. Furthermore, ATP binding and/or hydrolysis by NBD2, but not NBD1, is required for MRP1 to shift from a high to low affinity substrate binding state. Its rotation is driven by the free energy obtained from ATP hydrolysis. It is expected that the proton shuttle mechanisms unraveled for hGBP1 apply to many classes of GTPases/ATPases that possess an optimally-arranged hydrogen bonding network, which connects the catalytic water to a proton acceptor. In the simulation of the ATP/apo state, we obsd., for the first time, conformers of the active site with the canonical geometry for an in-line nucleophilic attack on the ATP γ-phosphate. of time-resolved FTIR data revealed two apparent rate consts. through robust numerical criteria. Using time-resolved crystallography, we show that hydrolysis of PPi is an intrinsic and critical step of the DNA synthesis reaction catalyzed by dPols. processes. NIH step (RDS) is proton transfer (PT) from the lytic water mol., which is strongly activated by a metaphosphate generated by a preceding Pγ-Oβ bond dissocn. and cutoff radii that are both computed from first principles. giving a picture of the electronic properties of the transition state (TS) for nucleophilic attack of water on the γ-PO3- group based on the structure of a RhoA/GAP-GDP-MgF3- TSA complex. Figure 1. Three-dimensional structures of members of the G protein superfamily are considered in light of other biochem. values, and their combination properly describes both membrane and protein structural properties. The results expose previously unobserved structural intermediates of the NBDs arising from asym. Differences in duty ratio can explain the diversity of structures, speeds and oligomerization states of members of the large kinesin, myosin and dynein families of motors. mechanics (QM/MM) studies of this step have been published, which have substantially contributed to the thinking about the catalytic mechanism. of substrates, indicating that Pdr5 is an uncoupled ABC transporter that constantly hydrolyzes ATP to ensure active substrate transport. structures have been well-characterized for various members of the kinesin family, not much is known about ATP hydrolysis inside the active site. m values for ATP and ITP hydrolysis are nearly identical, so these interactions are not likely to play a large role in recognition, with antigen processing (TAP) plays an important role in intracellular peptide transport from the mitochondrial matrix of Saccharomyces cerevisiae. at ∼1°, and reproduces exptl. The popular AMBER force field has parameters for monophosphates, but they do not extend well to polyphorylated mols. ATP-binding cassette (ABC) systems are universally distributed among living organisms and function in many different aspects of bacterial physiol. The present work clarifies the above point by considering the hydrolysis of phosphate monoesters. We propose a rotation of an O-H bond in the transition between two pentacoordinated structures, during which an overall transition state was identified with an activation energy of 50 kcal/mol. A review. Based on the modified Perdew and Wang exchange functional (MPW) and Becke's 1995 correlation functional (B95), we developed two hybrid meta d. functional theory (HMDFT) methods, namely MPW1B95 and MPWB1K. Molecular Mechanism of ATP Hydrolysis in an ABC Transporter, Biological phosphoryl-transfer reactions: understanding mechanism and catalysis, DOI: 10.1146/annurev-biochem-060409-092741, Biological phosphoryl-transfer reactions: Understanding mechanism and catalysis,,, Molecular motors: structural adaptations to cellular functions,, Rotation of F1-ATPase: how an ATP-driven molecular machine may work, DOI: 10.1146/annurev.biophys.33.110502.132716, Rotation of F1-ATPase: How an ATP-driven molecular machine may work, Annual Review of Biophysics and Biomolecular Structure,, G protein mechanisms: insights from structural analysis,, Structure, function, and evolution of bacterial ATP-binding cassette systems, Microbiology and Molecular Biology Reviews,,, ATP hydrolysis in water – a density functional study, ATP Hydrolysis in Water - A Density Functional Study,, On the mechanism of hydrolysis of phosphate monoesters dianions in solutions and proteins,, On the interpretation of the observed linear free energy relationship in phosphate hydrolysis: a thorough computational study of phosphate diester hydrolysis in solution, On the Interpretation of the Observed Linear Free Energy Relationship in Phosphate Hydrolysis: A Thorough Computational Study of Phosphate Diester Hydrolysis in Solution,, Mechanistic insights into the hydrolysis of a nucleoside triphosphate model in neutral and acidic solution, Mechanistic Insights into the Hydrolysis of a Nucleoside Triphosphate Model in Neutral and Acidic Solution,, Exploring the multidimensional free energy surface of phosphoester hydrolysis with constrained QM/MM dynamics, Exploring the Multidimensional Free Energy Surface of Phosphoester Hydrolysis with Constrained QM/MM Dynamics, Journal of Chemical Theory and Computation,, Quantum and classical dynamics simulations of ATP hydrolysis in solution, Quantum and Classical Dynamics Simulations of ATP Hydrolysis in Solution,, Addressing open questions about phosphate hydrolysis pathways by careful free energy mapping, Addressing Open Questions about Phosphate Hydrolysis Pathways by Careful Free Energy Mapping,, Modeling the mechanisms of biological GTP hydrolysis,, Adenosine triphosphate hydrolysis mechanism in kinesin studied by combined quantum-mechanical/molecularmechanical metadynamics simulations, Adenosine triphosphate hydrolysis mechanism in kinesin studied by combined quantum-mechanical/molecular-mechanical metadynamics simulations,, Advances in quantum simulations of ATPase catalysis in the myosin motor,, Unraveling the mystery of ATP hydrolysis in actin filaments,, Simulating protein mediated hydrolysis of ATP and other nucleoside triphosphates by combining QM/MM molecular dynamics with advances in metadynamics, Simulating Protein Mediated Hydrolysis of ATP and Other Nucleoside Triphosphates by Combining QM/MM Molecular Dynamics with Advances in Metadynamics,, Converting conformational changes to electrostatic energy in molecular motors: the energetics of ATP synthase, Converting conformational changes to electrostatic energy in molecular motors: The energetics of ATP synthase, Proceedings of the National Academy of Sciences of the United States of America,, On the mechanism of ATP hydrolysis in F1- ATPase, On the mechanism of ATP hydrolysis in F1-ATPase,, Double-lock ratchet mechanism revealing the role of αSER-344 in F, Double-lock ratchet mechanism revealing the role of αSer-344 in FoF1 ATP synthase,, Molecular mechanism of ATP hydrolysis in F, Molecular Mechanism of ATP Hydrolysis in F1-ATPase Revealed by Molecular Simulations and Single-Molecule Observations,, The hydrolysis activity of adenosine triphosphate in myosin: a theoretical analysis of anomeric effects and the nature of the transition state, The Hydrolysis Activity of Adenosine Triphosphate in Myosin: A Theoretical Analysis of Anomeric Effects and the Nature of the Transition State,, Resolving apparent conflicts between theoretical and experimental models of phosphate monoester hydrolysis, Resolving Apparent Conflicts between Theoretical and Experimental Models of Phosphate Monoester Hydrolysis,, Phosphate release in F1-ATPase catalytic cycle follows ADP release,,, ABC transporters: a riddle wrapped in a mystery inside an enigma,,, Mechanistic diversity in ATP-binding cassette (ABC) transporters,, Structural basis of energy transduction in the transport cycle of MsbA, Structural Basis of Energy Transduction in the Transport Cycle of MsbA, American Association for the Advancement of Science,, Alternating access of the putative substrate-binding chamber in the ABC transporter MsbA, Alternating Access of the Putative Substrate-Binding Chamber in the ABC Transporter MsbA,, Conformational dynamics of the nucleotide binding domains and the power stroke of a heterodimeric ABC transporter,, Snapshots of the maltose transporter during ATP hydrolysis,, H-loop histidine catalyzes ATP hydrolysis in the E. coli ABC-transporter HlyB,, A common mechanism for ATP hydrolysis in ABC transporter and helicase superfamilies,, Cooperative, ATPdependent association of the nucleotide binding cassettes during the catalytic cycle of ATP-binding cassette transporters, Cooperative, ATP-dependent association of the nucleotide binding cassettes during the catalytic cycle of ATP-binding cassette transporters, American Society for Biochemistry and Molecular Biology,, The conserved glutamate residue adjacent to the Walker-B motif is the catalytic base for ATP hydrolysis in the ATP-binding cassette transporter BmrA, The Conserved Glutamate Residue Adjacent to the Walker-B Motif Is the Catalytic Base for ATP Hydrolysis in the ATP-binding Cassette Transporter BmrA,, Catalytic mechanism of the maltose transporter hydrolyzing ATP, Catalytic Mechanism of the Maltose Transporter Hydrolyzing ATP,, ATP hydrolysis mechanism in a maltose transporter explored by QM/MM metadynamics simulation,, The E. coli BtuCD structure: a framework for ABC transporter architecture and mechanism, The E. coli BtuCD structure: A framework for ABC transporter architecture and mechanism,, Asymmetry in the structure of the ABC transporter-binding protein complex BtuCDBtuF, Asymmetry in the Structure of the ABC Transporter-Binding Protein Complex BtuCD-BtuF,, Asymmetric states of vitamin B12 transporter BtuCD are not discriminated by its cognate substrate binding protein BtuF,, Structure of AMP-PNP-bound vitamin B12 transporter BtuCD-F,, Structure of AMP-PNP–bound BtuCD and mechanism of ATP-powered vitamin B12 transport by BtuCD–F, Structure of AMP-PNP-bound BtuCD and mechanism of ATP-powered vitamin B12 transport by BtuCD-F,, Exceptionally large entropy contributions enable the high rates of GTP hydrolysis on the ribosome, Hybrid meta density functional theory methods for thermochemistry, thermochemical kinetics, and noncovalent interactions: the MPW1B95 and MPWB1K models and comparative assessments for hydrogen bonding and van der Waals interactions, Hybrid Meta Density Functional Theory Methods for Thermochemistry, Thermochemical Kinetics, and Noncovalent Interactions: The MPW1B95 and MPWB1K Models and Comparative Assessments for Hydrogen Bonding and van der Waals Interactions,, Benchmarking of DFT functionals for the hydrolysis of phosphodiester bonds, Benchmarking of DFT Functionals for the Hydrolysis of Phosphodiester Bonds,, Exploring conformational equilibria of a heterodimeric ABC transporter, Atomistic mechanism of large-scale conformational transition in a heterodimeric ABC exporter, Atomistic Mechanism of Large-Scale Conformational Transition in a Heterodimeric ABC Exporter,, ATP binding enables substrate release from Multidrug Resistance Protein 1, ATP Binding Enables Substrate Release from Multidrug Resistance Protein 1,, Release of entropic spring reveals conformational coupling mechanism in the ABC transporter BtuCD-F,, Role of the D-loops in allosteric control of ATP hydrolysis in an ABC transporter, Role of the D-Loops in Allosteric Control of ATP Hydrolysis in an ABC Transporter,, 19F NMR and DFT Analysis Reveal Structural and Electronic Transition State Features for RhoA-Catalyzed GTP Hydrolysis,, The GTPase hGBP1 converts GTP to GMP in two steps via proton shuttle mechanisms,, Elucidating the GTP hydrolysis mechanism in FeoB: a hydrophobic amino-acid substituted GTPase, Elucidating the GTP Hydrolysis Mechanism in FeoB: A Hydrophobic Amino-Acid Substituted GTPase,, Role of carboxylate residues adjacent to the conserved core Walker B motifs in the catalytic cycle of Multidrug Resistance Protein 1 (ABCC1), Role of Carboxylate Residues Adjacent to the Conserved Core Walker B Motifs in the Catalytic Cycle of Multidrug Resistance Protein 1 (ABCC1),, Properties of P-glycoprotein with mutations in the catalytic carboxylate glutamate residues, Properties of P-glycoprotein with Mutations in the "Catalytic Carboxylate" Glutamate Residues,, Distinct structural and functional properties of the ATPase sites in an asymmetric ABC transporter,, In vitro functional characterization of BtuCD-F, the Escherichia coli ABC transporter for vitamin B12 uptake, In Vitro Functional Characterization of BtuCD-F, the Escherichia coli ABC Transporter for Vitamin B12 Uptake,, H662 is the linchpin of ATP hydrolysis in the nucleotide-binding domain of the ABC transporter HlyB,, Time-resolved Fourier transform infrared spectroscopy of the nucleotide-binding domain from the ATP-binding cassette transporter MsbA: ATP hydrolysis is the rate-limiting step in the catalytic cycle, Time-resolved Fourier Transform Infrared Spectroscopy of the Nucleotide-binding Domain from the ATP-binding Cassette Transporter MsbA,, The ATP hydrolysis cycle of the nucleotide-binding domain of the mitochondrial ATP-binding cassette transporter Mdl1p,, Engineering ATPase activity in the isolated ABC cassette of human TAP1, Engineering ATPase Activity in the Isolated ABC Cassette of Human TAP1,, A mutation of the H-loop selectively affects rhodamine transport by the yeast multidrug ABC transporter Pdr5,, Classification and evolution of P-loop GTPases and related ATPases,, The structure of nonvertebrate actin: implications for the ATP hydrolytic mechanism, The structure of nonvertebrate actin: Implications for the ATP hydrolytic mechanism,, Comparing the catalytic strategy of ATP hydrolysis in biomolecular motors,, Comparison of multiple Amber force fields and development of improved protein backbone parameters, Proteins: Structure, Function, and Bioinformatics,, Improved side-chain torsion potentials for the Amber ff99SB protein force field,, Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature,, Membrane protein simulations using AMBER force field and Berger lipid parameters, Membrane Protein Simulations Using AMBER Force Field and Berger Lipid Parameters,, Development of an improved four-site water model for biomolecular simulations: TIP4P-Ew,, Development of polyphosphate parameters for use with the AMBER force field,, Improved treatment of ligands and coupling effects in empirical calculation and rationalization of pKa values, Improved Treatment of Ligands and Coupling Effects in Empirical Calculation and Rationalization of pKa Values,, PROPKA3: consistent treatment of internal and surface residues in empirical pKa predictions, PROPKA3: Consistent Treatment of Internal and Surface Residues in Empirical pKa Predictions,, pH of the cytoplasm and Periplasm of Escherichia coli: rapid measurement by green fluorescent protein fluorimetry, pH of the cytoplasm and periplasm of Escherichia coli: rapid measurement by green fluorescent protein fluorimetry,, GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation, GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation,, A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-Pu,, A combined quantum-mechanical and molecularmechanical potential for molecular dynamics simulations, A combined quantum mechanical and molecular mechanical potential for molecular dynamics simulations,, Canonical sampling through velocity rescaling,, P-LINCS: a parallel linear constraint solver for molecular simulation, P-LINCS: A Parallel Linear Constraint Solver for Molecular Simulation,, SETTLE: an analytical version of the SHAKE and RATTLE algorithm for rigid water models, SETTLE: an analytical version of the SHAKE and RATTLE algorithm for rigid water models,, Classical statistical mechanics of constraints: a theorem and application to polymers,, A new concise expression for the free energy of a reaction coordinate,, Determining the shear viscosity of model liquids from molecular dynamics simulations,